Impact of withdrawal of antiepileptic medication on the duration of focal onset seizures.

PURPOSE: To systematically evaluate the duration of focal onset seizures under medication withdrawal as a function of drug half-life. METHODS: Adults with drug resistant focal epilepsy and invasive electroencephalographic (iEEG) recording between 01/2006 and 06/2016 (n = 128) were identified. Patients with multifocal or unknown epileptic foci were excluded, as well as subclinical seizures, isolated auras, or status epileptic. Antiepileptic drugs (AEDs) were withdrawn upon admission. The seizure duration was determined based on the invasive EEG data, and the latency since start of the monitoring was noted in hours. A negative binomial mixed model was used to compare the seizure durations before and after a cut-off, which was set at 2.5 half-lives of the individual anticonvulsive medication as this is thought to separate therapeutic and ineffective drug levels. RESULTS: In total, 70 patients were included in the study and the duration of 672 seizures analyzed. On average, the patients were treated with 2.36 ± 0.78 AEDs. The individual cut-off of 2.5 half-lives was on average reached after 95.02 ± 80.18 h. The seizure frequency (321 vs. 351) and the rate of generalization (15.6% vs. 16.8%) was comparable before and after the individual cut-off point. The mean seizure duration was not statistically significantly prolonged after 2.5 half-lives by a factor of 1.168 for focal onset seizures (p = 0.090) and a factor of 1.091 for secondary generalized seizures (p = 0.545). CONCLUSIONS: Although AED withdrawal increases the likelihood for epileptic seizures, it did not prolong the seizure duration, nor did it increase the rate of secondary generalization in our study.

Quantitative and qualitative analysis of ictal vocalization in focal epilepsy syndromes.

PURPOSE: To investigate the frequency, localizing significance, and intensity characteristics of ictal vocalization in different focal epilepsy syndromes. METHODS: Up to four consecutive focal seizures were evaluated in 277 patients with lesional focal epilepsy, excluding isolated auras and subclinical EEG seizure patterns. Vocalization was considered to be present if observed in at least one of the analyzed seizures and not being of speech quality. Intensity features of ictal vocalization were analyzed in a subsample of 17 patients with temporal and 19 with extratemporal epilepsy syndrome. RESULTS: Ictal vocalization was observed in 37% of the patients (102/277) with similar frequency amongst different focal epilepsy syndromes. Localizing significance was found for its co-occurrence with ictal automatisms, which identified patients with temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative analysis of vocalization intensity allowed to distinguish seizures of frontal from temporal lobe origin based on the intensity range (p = 0.0003), intensity variation (p < 0.0001), as well as the intensity increase rate at the beginning of the vocalization (p = 0.003), which were significantly higher in frontal lobe seizures. No significant difference was found for mean intensity and mean vocalization duration. CONCLUSIONS: Although ictal vocalization is similarly common in different focal epilepsies, it shows localizing significance when taken into account the co-occurring seizure semiology. It especially increases the localizing value of automatisms, predicting a temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative parameters of the intensity dynamic objectively distinguished frontal lobe seizures, establishing an observer independent tool for semiological seizure evaluation.

[Digital electroencephalography in brain death diagnostics : Technical requirements and results of a survey on the compatibility with medical guidelines of digital EEG systems from providers in Germany]. / Digitale Elektroenzephalographie in der Hirntoddiagnostik : Technische Anforderungen und Ergebnisse einer Umfrage zur Richtlinienkompatibilität digitaler EEG-Systeme bei Anbietern in Deutschland.

BACKGROUND: The guidelines of the German Medical Association and the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) require a high procedural and technical standard for electroencephalography (EEG) as an ancillary method for diagnosing the irreversible cessation of brain function (brain death). Nowadays, digital EEG systems are increasingly being applied in hospitals. So far it is unclear to what extent the digital EEG systems currently marketed in Germany meet the guidelines for diagnosing brain death. METHODS: In the present article, the technical und safety-related requirements for digital EEG systems and the EEG documentation for diagnosing brain death are described in detail. On behalf of the DGKN, the authors sent out a questionnaire to all identified distributors of digital EEG systems in Germany with respect to the following technical demands: repeated recording of the calibration signals during an ongoing EEG recording, repeated recording of all electrode impedances during an ongoing EEG recording, assessability of intrasystem noise and galvanic isolation of measurement earthing from earthing conductor (floating input). RESULTS: For 15 of the identified 20 different digital EEG systems the specifications were provided by the distributors (among them all distributors based in Germany). All of these EEG systems are provided with a galvanic isolation (floating input). The internal noise can be tested with all systems; however, some systems do not allow repeated recording of the calibration signals and/or the electrode impedances during an ongoing EEG recording. CONCLUSION: The majority but not all of the currently available digital EEG systems offered for clinical use are eligible for use in brain death diagnostics as per German guidelines.

[Importance of imaging diagnostics and EEG for differential diagnosis of epileptic seizures]. / Bildgebende Diagnostik und EEG in der Differenzialdiagnose epileptischer Anfälle.

Electroencephalography (EEG) and neuroimaging are the two most crucial diagnostic methods for epilepsy. The EEG represents the only specific method to detect epileptogenicity of a brain lesion. The EEG shows some syndrome-specific alterations, helps to make therapeutic decisions and allows prognosis about the disease. Neuroimaging in epilepsy includes magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Neuroimaging is crucial to clarify the underlying etiology and to localize the epileptogenic zone and has contributed to expanding the spectrum of patients where epilepsy surgery can be provided. Both EEG and neuroimaging are valuable methods in the hands of experienced epileptologists but both can also be misdiagnosed and lead to a wrong diagnosis and treatment decisions. This review discusses the contribution of both methods, their potential role and limitations and shows typical examples of wrong interpretation.

[Diagnosis of non-epileptic paroxysmal disorders and epileptic seizures]. / Diagnose nichtepileptischer paroxysmaler Störungen und epileptischer Anfälle.

Non-epileptic paroxysmal disorders may clinically manifest in a similar way to epileptic seizures and have to be considered in the differential diagnosis of epilepsy. Syncope, non-epileptic psychogenic seizures, paroxysmal movement disorders, migraine, transient ischemic attacks and parasomnia constitute the major differential diagnoses. A meticulous history and a third party description are useful for the differential diagnosis. Neurological, psychiatric and cardiological examinations are required for the correct differential diagnosis. The interictal electroencephalogram (EEG), which is normal in non-epileptic patients, is frequently normal in epileptic patients at the onset of seizures, but reaches a high sensitivity after repeated recordings. In equivocal cases EEG video monitoring and in the case of suspected cardiac asystole, event recorders are useful diagnostic tools.

What is the "L" in LPDs? Localized as well as lateralized.

BACKGROUND: Periodic discharges (PDs) are well established as either periodic lateralized epileptiform discharges (LPDs) or generalized discharges. However, PDs in the midline can currently not be adequately classified as they are not generalized and not lateralized. AIMS OF THE STUDY: To propose a modification of the current LPD classification. METHODS: We here present a paradigmatic case series of three adult patients with midline LPDs. RESULTS: In our patients, ictal electroencephalography (EEG) recordings revealed periodic epileptiform discharges in the midline region. All three patients were non-lesional. CONCLUSION: We, thus, suggest to include periodic localized non-lateralized epileptiform discharges into the term LPDs (in addition to periodic lateralized epileptiform discharges), as they can also be recorded as localized EEG phenomenon in the midline region.

Intermediate latency evoked potentials of cortical multimodal vestibular areas: acoustic stimulation.

OBJECTIVE: Loud acoustic stimuli at 500Hz activate the vestibular system. Intermediate-latency vestibular cortical potentials of multimodal cortex regions were investigated, beyond the 20ms time range. METHODS: Eighteen healthy subjects with 32-channel EEG and one epilepsy patient with right-sided intracortical electrodes received three types of stimuli: tone bursts capable of evoking vestibular evoked myogenic potentials (VEMP) in neck muscles and sham stimuli matched for either frequency or amplitude, which cannot evoke myogenic responses. RESULTS: VEMP-capable stimuli activated anterior insula and posterior operculum bilaterally at 20, 30, 60 and 110ms, frontal brain regions at 70 and 110ms, determined by Brain Evoked Source Analysis BESA. Recordings from intracranial electrodes revealed corresponding peaks at identical latencies. Stimulus-locked high and low beta and mu band modulations were found in vestibular, parietal and occipital regions, beyond 20ms. Sham stimuli only evoked late acoustic potentials. Corresponding vestibular potentials were also seen in an eight-channel bipolar Laplacian montage. CONCLUSIONS: The sequentially appearing cortical potentials evoked by VEMP-capable stimuli co-locate with data from functional imaging studies. Frequency-specific activity (induced potentials) in these areas may reflect multimodal proprioceptive and visual sensory crosstalk. SIGNIFICANCE: Vestibular cortical evoked potentials may see clinical use in vertigo disorders.

[Classification of epileptic seizures and syndromes]. / Klassifikation epileptischer Anfälle und Syndrome.

Advances in diagnostic and therapeutic options require a revision of the current classification of seizures and epilepsies. Recently, a classification proposal was introduced which reflects the ambivalence of the Internationalen Liga gegen Epilepsie (ILAE). We suggest that epileptology should utilize the same established systematic approach used in clinical neurology.

[Epilepsy surgery]. / Epilepsiechirurgie.

Epilepsy surgery is an important therapeutic option for patients with epilepsy since one third of all epilepsy patients will still not be become seizure free despite newly developed antiepileptic drugs. Anterior temporal lobe resection is the most common procedure. Extratemporal resections require more complex diagnostics and often invasive evaluation which is not the case in most temporal epilepsy patients due to improved imaging (MRI, PET, SPECT). Electrical stimulation of the anterior thalamus has been available as a treatment option since last year.

[Differential diagnosis of epileptic seizures]. / Differenzialdiagnose epileptischer Anfälle.

The differential diagnoses of epileptic seizures depend on the different semiologies of the respective seizures. Patient history and history of witnesses are of foremost importance in the differentiation. When seizures recur, they are more easily distinguished than single seizures. Diagnostic methods like EEG and eventually EEG video monitoring will help in the differentiation when clinical information and patient history do not allow a clear diagnosis. We present the most common differential diagnoses and their differences compared to epileptic seizures.

[Significance of the EEG in the diagnosis of epilepsy]. / Bedeutung des EEG in der Epilepsiediagnostik.

The electroencephalogram (EEG) is a specific diagnostic method for the evaluation of patients with epilepsies. Interictal epileptiform discharges (IED) recorded in the seizure interval have a high association with the clinical diagnosis of epilepsy. IEDs have to be differentiated from normal variants that resemble IEDs. The EEG may help in the localization of the epileptogenic zone and in the syndrome classification, which is important for therapy and prognosis.

Congruence and discrepancy of interictal and ictal EEG with MRI lesions in focal epilepsies.

OBJECTIVE: To compare the occurrence and localization of interictal epileptiform discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of MRI lesions. METHODS: We retrospectively analyzed the EEG and MRI data of a series of patients with focal epilepsies that had been studied from 1991 to 2009. RESULTS: In patients with temporal lesions, the localization of IEDs was most congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5% with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto-occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe compared to 48.5% with no parieto-occipital IEDs at all. Patients with central lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization of ESPs also differed between the regions. They were most congruent in temporal lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the majority of ESPs over the lesional lobe), which differed from frontal and parieto-occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional lobe). Patients with central lesions had ESPs very frequently only outside the lesional lobe (63.6%). Surgery outcome did not differ between the regions. CONCLUSIONS: The occurrence and localization of interictal and ictal EEG findings differs vastly for lesions in different brain regions. These findings should be used to carefully weigh the results from EEG studies particularly in patients with extratemporal epilepsies considered for epilepsy surgery.

Dysprosody during epileptic seizures lateralizes to the nondominant hemisphere.

OBJECTIVE: In human speech, the changes in intonation, rhythm, or stress reflect emotions or intentions and are called prosody. Dysprosody is the impairment of prosody and has been described in stroke and neurodegenerative disorders. Reports in epilepsy patients are limited to case reports. METHODS: We assessed prosody qualitatively and quantitatively in 967 focal epilepsy patients. The qualitative assessment was performed by 2 native German speakers, and the quantitative frequency analysis used linguistic software tools. For the quantitative analysis, the formant F0 (a frequency peak, which is an approximation of pitch) and the further spectral frequency peaks of our patients' voices were analyzed. RESULTS: We found 26 patients with ictal dysprosody through qualitative analysis (2.7% of all focal epilepsies). The qualitative changes affected mostly the pitch and the loss of melody. The seizure patterns at the time of ictal dysprosody were always in the nondominant hemisphere (100%) and were mostly right temporal (n = 22; 84.6%). Quantitative analysis of 15 audio samples (11 patients) showed a change in the frequency of formant F0 of several patients and a reduction of frequency variation during ictal speech, expressed as the SD of formant F0 (ictal 14.1 vs interictal 27.2). CONCLUSIONS: Ictal dysprosody localizes seizure onset or propagation to the nondominant temporal lobe. This information can be used in the evaluation of patients considered for resective epilepsy surgery.

Differences in corpus callosum volume and diffusivity between temporal and frontal lobe epilepsy.

We analyzed volume and diffusivity measures of the corpus callosum (CC) in patients with temporal (TLE) and frontal (FLE) lobe epilepsy in comparison with healthy subjects. On high-resolution T1-weighted scans of 18 controls and 44 patients the volumes (cm(3)) of Witelson regions (WRs) and the entire CC were measured. The apparent diffusion coefficients (ADCs, 10(-5)mm(2)s(-1)) for the entire CC and three areas of interest were measured from co-registered ADC maps. The CC of patients with TLE and FLE, corrected for total brain volume, was smaller than that of controls. Patients' ADC values were higher than those of controls. Findings were significant for WR1, WR2, and WR6, the CC regions connecting the frontal and temporal lobes. Patients with FLE had smaller WR1 and higher ADC values; in patients with TLE, the findings were similar for WR6. Atrophy and increased diffusivity in subregions of the CC connecting homotopic contralateral cortical regions indicate anatomical abnormalities extending beyond the epileptogenic zone in FLE and TLE.

14 & 6Hz positive spikes coinciding with PLEDs.

OBJECTIVE: We describe the coincidence of 14 & 6Hz positive spikes with PLEDs in a patient with clonic status epilepticus of the left upper extremity and the persistence of 14 & 6Hz positive spikes after cessation of status. METHODS: Digital video-EEG recordings were performed using 32-channel EEG equipment (XLTEK, Canada) with all electrodes of the international 10-20 system and additional anterior temporal electrodes in a patient during clonic status epilepticus and 2 months later after cessation of status. RESULTS: The initial EEG during clonic status epilepticus showed right hemispheric PLEDs and right lateral temporal 14 & 6Hz positive spikes in between the PLEDs. Follow up EEG recording 2 months later after cessation of status revealed an absence of PLEDs, a continuous slowing over the right hemisphere and the occipital background of 7Hz. Right lateral temporal 14 & 6Hz positive spikes were recorded in the same frequency and the same localization as in the previous status EEG. CONCLUSIONS: This case demonstrates that a hemisphere which is in a status epilepticus as clinically reflected by clonic status of the left hand and PLEDs in the EEG is still capable to produce a benign variant pattern like 14 & 6Hz positive spikes. SIGNIFICANCE: The generator of 14 & 6Hz positive spikes may still persist despite the presence of severe structural and epileptogenic lesions in the same hemisphere.